Incidence, clinical features and perinatal outcome in anomalous fetuses with late-onset growth restriction: cohort study

Objective: To describe the incidence, clinical features and perinatal outcome of late onset growth restriction (FGR) associated with genetic syndromes or aneuploidy, structural malformation, or congenital infection. Methods: Retrospective multicenter cohort study conducted at four tertiary maternity hospitals in Italy. We included singleton pregnancies between 32+0 and 36+6 weeks of gestation with either abdominal circumference or estimated fetal weight <10 percentile for gestational age or a reduction by over 50 percentiles of abdominal circumference from an ultrasound scan performed between 18 and 32 weeks of gestation. The study group included pregnancies where FGR was associated with a genetic syndrome or aneuploidy, structural malformation, or congenital infection, i.e. anomalous late-onset FGR; the control group consisted of pregnancies with structurally and genetically normal late-onset FGR. Composite adverse perinatal outcome was defined by the presence of any among stillbirth, Apgar score <7 at 5 minutes, NICU admission, need for respiratory support at birth, neonatal jaundice and neonatal hypoglycemia. Results: Overall, 1246 pregnancies complicated by late-onset FGR were included, of which 120 (9.6%) were allocated to the anomalous late-onset FGR group. Of these, 11 (0.9%) had a genetic syndrome or aneuploidy, 105 (8.4%) isolated structural malformation, and 4 (0.3%) congenital infection. The most frequent structural defects associated with late-onset anomalous FGR were genitourinary malformations (28/105, 26.7%), and skeletal anomalies (21/105, 20%). Compared to the non-anomalous group, anomalous late onset FGR fetuses were associated with an increased incidence of composite adverse perinatal outcome (58.3% vs 35.9%; p<0.01). Anomalous late-onset FGR newborns showed a higher frequency of need for respiratory support at birth (25.8% vs 9.0%; p<0.001), intubation (10.0% vs 1.1%; p<0.01), intensive care unit (NICU) admission (43.3% vs 22.2% p<0.01) and longer length of hospital stay (24 (4-250) days vs 11 (2-59) days, p<0.01). Conclusions: Most pregnancies complicated by anomalous late-onset FGR fetuses are associated with structural malformations. Anomalous late-onset FGR fetuses are associated with an increased incidence of complications at birth and NICU admission and a longer length of hospital stay compared to isolated late-onset FGR fetuses.